1. Technical Field
The invention relates to methods and materials for evaluating rheumatoid arthritis as well as for determining an individual's predisposition to have severe rheumatoid arthritis disease.
2. Background Information
Rheumatoid arthritis (RA) affects individuals in the prime of their life and is feared because of its potential to cause chronic pain and irreversible damage of tendons, ligaments, joints, and bones. The symmetrical involvement of small peripheral joints has an enormous impact on hand and foot functions and poses therapeutic challenges that cannot be easily overcome by joint replacement. Also, systemic manifestations of RA are not rare and can range from relatively minor problems, such as rheumatoid nodules, to life-threatening organ disease.
In addition, RA is a systemic inflammatory disease that primarily manifests itself as synovial inflammation of diarthrodial joints. The typical histopathological changes include dense infiltration of the synovial membrane by mononuclear cells, neoangiogenesis, and hypertrophy and hyperplasia of the synovial lining (Harris ED (ed); Rheumatoid Arthritis, Philadelphia, WB Saunders Co., pp.3-212 (1997); and Hale L P, Haynes B F: Pathology of rheumatoid arthritis and associated disorders. Arthritis and Allied Conditions. A textbook of Rheumatology. Edited by Koopman W J. Baltimore, Williams & Wilkins, pp.993-1016 (1997)). The etiopathogenesis of the syndrome is not understood. Several lines of evidence support a central role of T lymphocytes in the disease-specific pathogenic events (Todd, et al. Science, 240:1003-1009 (1988); Panayi, et al., Arthritis Rheum, 35:729-735 (1992); and Goronzy J J, Weyand C M: Rheum Dis Clin North Am, 21:655-674 (1995)). An alternative hypothesis, namely, that macrophages are the pivotal cell type in rheumatoid synovitis, has also been proposed (Firestein G S, Zvaifler N J: Arthritis Rheum 33:768-773 1990); and Burmester, et al., Arthritis Rheum, 40:5-18 (1997)). Whether only T cells or only macrophages or both are the causative elements in RA remains a matter of controversy (Feldmann, et al., Cell, 85:307-310 (1996); and Fox, Arthritis Rheum 40:598-609 (1997)).
RA is primarily a clinical diagnosis. Symmetrical joint involvement, dominant manifest ations in peripheral joints, rheumatoid factor production, and the formation of rheumatoid nodules are considered when the diagnosis is made (Arnett, et al., Arthritis Rheum. 31:315-324 (1988)). The histological appearance of the synovium varies quite extensively and the pathological findings are usually not helpful in distinguishing RA from other inflammatory athropathies (Hale L P, Haynes B F: Pathology of rheumatoid arthritis and associated disorders. Arthritis and Allied Conditions. A textbook of Rheumatology. Edited by Koopman W J. Baltimore, Williams & Wilkins, pp.993-1016(1997)). In addition, no information is available on the mechanisms underlying the topographical arrangement of the inflammatory infiltrate in the rheumatoid synovium.
Therapeutic management of RA has steadily improved over the last decades, mostly due to the recognition that destruction caused by chronic inflammation is irreversible and that only early and aggressive intervention can enhance therapeutic benefit. Consequently, RA patients are now being treated early in the disease course and disease modifying agents are widely used. Despite these successes, major challenges remain. Presently, no curative intervention is available, side effects of therapies are significant, and the disease may still progress while the patient is being treated.